Human papilloma virus (HPV) is a kind of DNA virus only hosted in skin and mucous complex squamous epithelia, and has not been cultured successfully outside of body. HPV induces a lot of benign papillary tumor or verruca of skin and mucous, some of which have latent carcinogenicity.
Nowadays, 120 types of HPV have been identified. The virus can be classed as skin type and genital meatus type according to their infected epithelia part on the body. About 35 types of HPV among them can infect the female genital meatus and about 20 types among them are related with the tumor. According to the dangerous degrees caused by different HPV types, HPV can be divided into high dangerous type and low dangerous type, low dangerous type includes for example: HPV6, 11, 42, 43, 44, CP8304 and the like, which induce benign lesions such as condyloma in genital meatus including (cervical intra-epithelial neoplasia) CIN-I. High dangerous types of HPV include HPV16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 68 and the like, which induce CIN-II, CIN-III and cervical cancer, it is especially this case for HPV16 and 18.
HPV infection is one of the most common infectious diseases that is transmitted by sex, and is related with sex life. It is believed by the person skilled in the art that HPV infection is the main factor of cervical cancer. HPV infection badly destroys the health of people, even results in death.
New infected cases may be about 10%-15% every year, based on the women all over the world. HPV infection is very common in many countries. Rate of incidence among young women having frequent sex is the highest; the peak age of infection is 18-28 years old. For most of the women, infective period is short, usually with 8-10 months. But there is still 10%-15% among women over 35 years old has a tendency of continuing infection. These continuous infected women are the high dangerous people of developing further into cervical cancer.
According to a related report, HPV infected people are 630 million in the world every year. 20 million of them are in the States of America. In addition, there are more than 5.5 million people who are diagnosed as HPV infection in America every year, in which more than one million are presented as wart of genitalia. HPV infection is becoming a public health problem.
According to the statistics made by the WHO, mortality induced by cervical cancer is in the second place among the death induced by cancer and in some developing countries it even is in the first place. There are more than 0.5 million cases of cervical cancer occurring every year, and about 0.2 million people are dead of cervical cancer, with 80% of them being in the developing country. Cervical cancer occupies 24% of the female malignant tumor in the developing country and 7% in the developed country. In the 21 st century, cervical cancer has become one of the severest diseases that destroy the health of women in the world.
According to an inadequate statistics, in China there are 138 thousand women who suffer from cervical cancer and about 50 thousand women who are dead of cervical cancer every year, which is 25% based on the total number of cases occurring all over the world. But what is afflictive to the doctors is that a lot of patients can only be diagnosed in the late period when the valuable early therapy period is missed because early screening methods is imperfective, and moreover, patients newly suffering from cervical cancer are younger.
Prevention and Treatment of HPV Infection
There is no special method to prevent this disease. Generally, cutting off the transmitting way according to HPV transmission type is effective.
Small marts induced by the HPV may subside spontaneously, so no treatment is needed.
However, it is necessary to make operation for treating condyloma acuminatum because of its large scale of damnification. This method, meanwhile, is usually with high relapse rate. Physical therapy like galvanocantery or laser therapy and the like may also be applied.
On one aspect, there is no effective method to cure HPV infection and no effective medicament to cure cervical cancer, but on the other aspect cervical cancer is the first one whose sepathology has been known, and whose screening method is flawless. So it is very possible to achieve early diagnosis and early treatment through general screening. Cervical cancer may be the first one to be cured by humankind.
Moreover, many countries mainly apply “vaccine” to prevent from and treat with cervical cancer. By using vaccine, especially by using special combinational immune vaccine to stimulate the strong immune reaction of body, it is possible to clean up HPV infection and cancer cells remained after operation.
Nowadays, vaccines used for treating or preventing HPV virus in the world include that:
1. Preventative vaccine is virus-like granule vaccine, used as the target antigen of HPV preventive vaccine, which is major capsid protein L1 and minor protein L2 of HPV. Since expression protein of L1 and L2 can self assemble to form virus-like granule which is similar with the natural virus granule in special structure and epitope without containing HPV DNA, Good immunity effects by carrying out lots of animal experiments have been obtained. Clinical trials I/II have been approved and the applicant plans to carry trials III/IV in Europe.
2. Vaccine with preventive and therapeutic activity is chimeric virus-like granule, which is E7 chimeric virus granule made by L1 capsid protein and E7 polypeptide, having preventing and therapeutic activity. The chimeric virus granule can not only stimulate the production of neutralizing antibody, but also induce stronger E7 special CTL reaction and anti-tumor activity in body. At present, one kind of chimeric virus granule vaccine including HPV16 type L1, L2 and E7 target antigen will be tested in the clinical phage Itrial
3. One kind of therapeutic vaccine is vaccinia carrier vaccine which is the most common virus carrier, used as vaccinia virus for killing human smallpox, and having long, large scale history of inoculation applied by human. A clinical trial I about Cervical Cancer therapy was carried out in England by using recombined vaccinia carrier vaccine and E6, E7 protein expressing HPV16 and HPV18. There is no any adverse effect is observed. In some patients being tested, special antibody can be detected, CTL reaction and cytokines, which are different from each other, and may be related with the phages of cancer. Disadvantage is inhibiting re-immunization.
4. Polypeptide vaccine is also a kind of therapeutic vaccine. In the researches about antigens, the epitope recognized by CTL is determined, which provides the chance for developing polypeptide vaccine. Therefore, it is possible to enhance the production of tumor special CTL by using HPV16 type E6 or E7 polypeptide to immune. The clinical experiment of using HPV polypeptide vaccine to resist HPV related tumor is in clinical trials I/II, and there is no obvious adverse effect is observed. Persons with different inheritance background should use different polypeptide vaccine matching with HLA.
5. DNA vaccine is also a kind of therapeutic vaccine. The function of DNA vaccine is leading expressing plasmid carrying purpose gene into the body, and causing special immune reaction by expressing antigen in vivo. At present, the gene of DNA vaccine for treating HPV is HPV 16 type E7 gene. This kind of vaccine working by muscular injection is in the clinical I/II phase test. The weak immunity activity and problem of safety of DNA vaccine in the body should be noted.
For the research on HPV vaccine in China, in the aspect of preventive vaccine, people have finished the construction of HPV16 type L1 and L1/L2 recombined bacilliform virus strain which has been expressed in insect cells; observation of the formation of virus granule under electric mirror; successful construction of recombined copy with L1/L2 expression and non-copy type poxvirus vaccine strain. In the aspect of therapeutic vaccine research, people have constructed the recombined copy type expressing HPV16 E6/E7 protein and non-copy type poxvirus vaccine strain.
In a word, treatment of HPV infection and cervical cancer with vaccine is desired, and is hopeful. But it will take a long time to be applied by clinical use. HPV causing the cervical disease includes a lot of types, but present study is only focused on HPV16 type. There still is some limitation in the use and inoculation is restricted by the age of patient. So it is desired to prepare better and safer medicament as well as better therapeutic method to cure the disease.
Nocardia Rubra Cell Wall Skeleton agent is a well-known medicament in the art. In the prior art it is used for anti-fungus treatment such as for treatment of infection caused by Candida albicans, or also used in treatment of cervical erosion and for anti-herpes simplex and anti-herpes zoster, and the like. But there is no any report about using it in the treatment of HPV infection.